Slides

Slide 2
Plasmodium falciparum is the most prevalent malaria parasite in sub-Saharan Africa, accounting for
99% of estimated malaria cases in 2016. Outside of Africa, P. vivax is the predominant parasite in the
WHO Region of the Americas, representing 64% of malaria cases, and is above 30% in the WHO South-
East Asia and 40% in the Eastern Mediterranean regions.

Most deaths are caused by P. falciparum because P. vivax, P. ovale, and P. malariae generally cause a milder form of malaria. The species P. knowlesi rarely causes disease in humans.

Slide 3
 - Funding: In 34 out of 41 high-burden countries, which rely mainly on external funding for malaria programmes,
the average level of funding available per person at risk in the past 3 years (2014–2016) reduced when
compared with 2011–2013. Exceptions were Democratic Republic of the Congo, Guinea, Mauritania,
Mozambique, Niger, Pakistan and Senegal, which recorded increases.
Among the 41 high-burden countries, overall, funding per person at risk of malaria remains below
US$ 2.

- Histidine-rich protein 2 deletions:
In some settings, increasing levels of histidine-rich protein 2 gene (HRP2) deletions threaten the ability
to diagnose and appropriately treat people infected with falciparum malaria. An absence of the HRP2
gene enables parasites to evade detection by HRP2-based Rapid Diagnosis Tests(RDTs), resulting in a false-negative test
result. Although the prevalence of HRP2 gene deletions in most high-transmission countries remains
low, further monitoring is required.

Distributions of malaria RDTs have increased, which
has helped to improve the accurate diagnosis of
malaria and thus increase the likelihood of appropriate
treatment. Ensuring the safety and quality of
the RDTs used in malaria control and case management
has been a major focus of WHO and its
partners. The tests that are most sensitive for detecting
falciparum malaria contain antibodies to detect
histidine-rich protein 2 (HRP2) or the related HRP3
protein. These protein targets, which are specific to
P. falciparum, are strongly expressed by asexual
parasites. About 10 years ago, researchers working
in the Amazon region of Peru identified patients
infected with P. falciparum strains in which the genes
that encode these proteins (pfhrp2 and pfhrp3) were
deleted (34), which meant the strains were not
detected with HRP2-based RDTs. Since then, such
strains have been found in other countries and
regions. The frequency and global distribution of this
phenomenon is not yet fully understood; however, in
a few countries, the relative incidence of these deletions
has been found to be high enough to threaten
the usefulness of HRP2-only RDTs.

The histidine-rich protein II (HRP II) is a histidine- and alanine-rich, water-soluble protein, which is localized in several cell compartments including the parasite cytoplasm. The antigen is expressed only by P. falciparum trophozoites. HRP II from P. falciparum has been implicated in the biocrystallization of hemozoin, an inert, crystalline form of ferriprotoporphyrin IX (Fe(3+)-PPIX) produced by the parasite. A substantial amount of the HRP II is secreted by the parasite into the host bloodstream and the antigen can be detected in erythrocytes, serum, plasma, cerebrospinal fluid and even urine as a secreted water-soluble protein.[11] These antigens persist in the circulating blood after the parasitaemia has cleared or has been greatly reduced. It generally takes around two weeks after successful treatment for HRP2-based tests to turn negative, but may take as long as one month, which compromises their value in the detection of active infection. False positive dipstick results were reported in patients with rheumatoid-factor-positive rheumatoid arthritis.[9] Since HRP-2 is expressed only by P. falciparum, these tests will give negative results with samples containing only P. vivax, P. ovale, or P. malariae; many cases of non-falciparum malaria may therefore be misdiagnosed as malaria negative (some P.falciparum strains also don’t have HRP II). The variability in the results of pHRP2-based RDTs is related to the variability in the target antigen.

- Drug Resistance:
■■Artemisinin-based combination therapies(ACTs) have been integral to the recent success of global malaria control,
and protecting their efficacy for the treatment of malaria is a global health priority.
■■Although multidrug resistance, including artemisinin (partial) resistance and partner drug resistance,
has been reported in five countries of the Greater Mekong subregion (GMS), there has been a massive
reduction in malaria cases and deaths in this subregion. Monitoring the efficacy of antimalarial drugs
has led to timely treatment policy updates across the GMS.
■■In Africa, artemisinin (partial) resistance has not been reported to date and first-line ACTs remain
efficacious in all malaria endemic settings.

- Insecticide resistance
■■ Of the 76 malaria endemic countries that provided data for 2010 to 2016, resistance to at least one
insecticide in one malaria vector from one collection site was detected in 61 countries. In 50 countries,
resistance to two or more insecticide classes was reported.
■■ In 2016, resistance to one or more insecticides was present in all WHO regions, although the extent of
monitoring varied.
■■ Resistance to pyrethroids – the only insecticide class currently used in insecticide-treated mosquito nets(ITNs) – is widespread.
The proportion of malaria endemic countries that monitored and subsequently reported pyrethroid
resistance increased from 71% in 2010 to 81% in 2016. The prevalence of confirmed resistance to
pyrethroids differed between regions, and was highest in the WHO African and Eastern Mediterranean
regions, where it was detected in malaria vectors in over two thirds of all sites monitored.
■■ ITNs continue to be an effective tool for malaria prevention, even in areas where mosquitoes have
developed resistance to pyrethroids. This was evidenced in a large multicountry evaluation coordinated
by WHO between 2011 and 2016, which did not find an association between malaria disease burden
and pyrethroid resistance across study locations in five countries.

slide 5
ACTs have been integral to the recent success of
global malaria control, and protecting their
efficacy for the treatment of malaria is a global
health priority. The main advantage of ACTs is that
the artemisinin quickly reduces most of the malaria
parasites and the partner drug clears the
remaining ones. However, the efficacy of ACTs is
threatened by the emergence of both artemisinin
and partner drug resistance. Partial resistance to
artemisinin causes delayed parasite clearance
following treatment with an ACT. Such resistance
does not usually lead to treatment failure; however,
if the artemisinin component is less effective, the
partner drug has to clear a greater parasite mass,
jeopardizing the future efficacy of the partner drug.
In addition, partner drug resistance can arise
independently of artemisinin resistance. Given that
an effective partner drug is essential for clearing all
remaining parasites, partner drug resistance
carries a high risk of treatment failure. Because of
their different roles, the efficacy of the artemisinin
and the partner drug must be monitored
concomitantly but separately.
For P. vivax, chloroquine (CQ) remains an effective
first-line treatment in many countries. Countries
endemic for vivax malaria recommend either CQ or
an ACT for treating uncomplicated P. vivax. Most also
include primaquine (PQ) to eliminate latent liver stage
infections and prevent relapse. In addition, PQ
improves the activity of CQ against CQ-resistant
blood stage parasites. Where there is a high treatment
failure rate with CQ (>10%), countries are encouraged
to change their first-line treatment to an ACT.

Artesunate and amodiaquine
Artesunate and mefloquine
Artemether and lumefantrine
Artesunate and sulfadoxine/pyrimethamine
Dihydroartemisinin-piperaquine (Duo-Cotecxin, or Artekin)
Artesinin/piperaguine/primaquine
Pyronaridine and artesunate



Phenyl propanoids and Lignans
Junior Murvin - Police and Thieves
Gregory Isaacs - Once Ago
Richie Spice - Earth A run Red